The purpose of this study is to examine the pathogenesis of the two major types of pigment gallstones: (1) Black stones which contain calcium salts of bilirubinate, pigment polymers, carbonates and phosphate a well as protein and (2) bilirubinate stones which contain predominantly calcium salts of bilirubinate and palmitate and other fatty acids with a small amount of protein. We have proposed that black stones form through entrapment of calcium salts by calcium-binding proteins while bilirubinate stones form secondary to stasis and/or infection which breaks down biliary lipids into components which become insoluable through precipitation with calcium. The aims of this project are: (1) characterize, quantitate and examine the regulation of protein synthesis and secretion using 3H glucosamine incorporation into gallbladder explants from guinea pigs and from patients with pigment and cholesterol gallstones. Studies include regulation of intra- and extracellular calcium, and effects on these properties of aging, lithogenic diet and stasis. (2) To utilize the non-invasive microanalytic techniques of 2-dimensional elemental microprobe analysis and ESCA surface analysis following argon and oxygen plasma etching, coupled with scanning electron microscopy to examine stone nidation and growth. (3) To examine stone composition utilizing Fourier transform infrared spectroscopy to answer previously unanswerable questions such as: the form of bilirubin in black stones, the distribution of bile acids between the center and periphery of gallstones and the location of proteins within stones.